title: A comparison of sex-specific immune signatures in Gulf War illness and chronic fatigue syndrome.
abstract: BACKGROUND
  Though potentially linked to the basic physiology of stress response we still have no clear understanding of Gulf War Illness (GWI), a debilitating condition presenting complex immune, endocrine and neurological symptoms. Here we compared male (n = 20) and female (n = 10) veterans with GWI separately against their healthy counterparts (n = 21 male, n = 9 female) as well as subjects with chronic fatigue syndrome/ myalgic encephalomyelitis (CFS/ME) (n = 12 male, n = 10 female).
  
  
  METHODS
  Subjects were assessed using a Graded eXercise Test (GXT) with blood drawn prior to exercise, at peak effort (VO2 max) and 4-hours post exercise. Using chemiluminescent imaging we measured the concentrations of IL-1a, 1b, 2, 4, 5, 6, 8, 10, 12 (p70), 13, 15, 17 and 23, IFNγ, TNFα and TNFβ in plasma samples from each phase of exercise. Linear classification models were constructed using stepwise variable selection to identify cytokine co-expression patterns characteristic of each subject group.
  
  
  RESULTS
  Classification accuracies in excess of 80% were obtained using between 2 and 5 cytokine markers. Common to both GWI and CFS, IL-10 and IL-23 expression contributed in an illness and time-dependent manner, accompanied in male subjects by NK and Th1 markers IL-12, IL-15, IL-2 and IFNγ. In female GWI and CFS subjects IL-10 was again identified as a delineator but this time in the context of IL-17 and Th2 markers IL-4 and IL-5. Exercise response also differed between sexes: male GWI subjects presented characteristic cytokine signatures at rest but not at peak effort whereas the opposite was true for female subjects.
  
  
  CONCLUSIONS
  Though individual markers varied, results collectively supported involvement of the IL-23/Th17/IL-17 axis in the delineation of GWI and CFS in a sex-specific way.
authors.affiliation: Department of Medicine, University of Alberta, Edmonton, AB, Canada.
authors.forename: Anne Liese
authors.initials: AL
authors.lastname: Smylie
authors.forename: Gordon
authors.initials: G
authors.lastname: Broderick
authors.forename: Henrique
authors.initials: H
authors.lastname: Fernandes
authors.forename: Shirin
authors.initials: S
authors.lastname: Razdan
authors.forename: Zachary
authors.initials: Z
authors.lastname: Barnes
authors.forename: Fanny
authors.initials: F
authors.lastname: Collado
authors.forename: Connie
authors.initials: C
authors.lastname: Sol
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Fletcher
authors.forename: Nancy
authors.initials: N
authors.lastname: Klimas
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D015331:Cohort Studies; D016207:Cytokines / Q000097:blood; D015673:Fatigue Syndrome, Chronic / Q000097:blood / Q000276:immunology*; D005260:Female; D047830:Gulf War; D006801:Humans; D008297:Male; D008875:Middle Aged; D018923:Persian Gulf Syndrome / Q000097:blood / Q000276:immunology*; D012727:Sex Characteristics
chemical_list: D016207:Cytokines